In recent years, parenteral nutrition has been widely practiced although its use is often accompanied by undesirable side effects such as infection, thrombosis, catheter and air embolization, and metabolic problems.
The use of parenteral nutrition has proved to be an extremely important tool in the treatment of a wide variety of diseases. For example, mortality from acute alimentary failure as in enterocutaneous fistula, has been considerably reduced by parenteral nutrition. Patients who have had extensive intestinal resection for such condition as Crohn's disease and ulcerative colitis have maintained good health at home for a long time on parenteral nutrition.
Parenteral nutrition also reduces the risks accompanying surgery in under-nourished patients, and promotes tissue repair and immune response following major surgery, trauma, and especially burns or multiple fractures with sepsis. Furthermore, short term parenteral nutrition has been lifesaving in comatose patients and in intractable anorexia nervosa. Support with parenteral nutrition has permitted chemotherapy and radiation therapy in patients with cancer otherwise considered unsuitable for any treatment.
However, even though parenteral nutrition has proved to be useful and necessary over the years, the concentrated fat emulsions that are used for the preparation of suitable solutions are mainly responsible for the various side effects that are encountered. Hence, the ideal source of calories for parenteral nutrition should have a high caloric density, a total solubility in water, no ionic charge, thus avoiding the necessity of administering a counter ion like Na.sup.+, good diffusibility through cell membranes to avoid hyperosmolality, rapid metabolism to acetyl-CoA and protein sparing action.
There are good reasons to believe that 1,3-butanediol, either as a DL mixture or as the D- or L-isomers can meet most of the above-mentioned criteria. The DL mixture has been investigated as a component of animal feed for a long time. When humans were fed a diet containing 5% of DL-1,3-butanediol, nitrogen was spared and there was no adverse effect. Furthermore, DL-1,3-butanediol alleviates the ethanol withdrawal syndrome in rats thus making it a potential therapeutic agent in human alcoholics. DL-1,3-butanediol is metabolised in the liver to DL-3-hydroxybutyrate via alcohol and aldehyde dehydrogenase; the D-.beta.-hydroxybutyrate is in oxydo-reduction equilibrium with acetoacetate via the action of D-.beta.-hydroxybutyrate dehydrogenase.
On the other hand, L-.beta.-hydroxybutyrate is not a natural compound although it is very well used by mammalian cells. In addition, it has been demonstrated that L-1,3-butanediol is useful in reducing the blood glucose level of alloxan-diabetic rats.
However, although the use of butanediol in parenteral nutrition and diabetic control looks promising, the use of this substance presents some drawbacks. First, butanediol has a low molecular weight. As a result from this, high amounts of butanediol must be employed in order to provide sufficient calory intake. Furthermore, butanediol is a strong reducing agent and there is a possibility of creating an oxidation-reduction imbalance if parenteral nutrition is to be maintained for a long period of time.
Therefore, a parenteral composition comprising a compound replacing the usually employed concentrated fat emulsion and having a high molecular weight, a proper oxidation-reduction balance, as well as minimal side effects would be highly desirable.